{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T00:57:25Z","timestamp":1794272245816,"version":"4.9.0"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Regulatory T cells (Tregs) play a pivotal role in maintaining immune homeostasis; however, their presence in the tumor microenvironment contributes to immune evasion and cancer progression. The modulation of Tregs has emerged as a key strategy in immunotherapy, with approaches ranging from direct depletion to functional reprogramming. This review summarizes advances in Treg modulation through checkpoint blockade, selective depletion, and metabolic or epigenetic reprogramming. Additionally, we discuss the potential of Treg plasticity as a therapeutic avenue, emphasizing how shifts in Treg phenotype can enhance antitumor immunity. Furthermore, we highlight combinatory strategies, including radiotherapy, cytokine-based therapies, and metabolic targeting that reshape the immune landscape to potentiate cancer immunotherapy. 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